Different Regimens of Transarterial Chemoembolization for Hepatocellular Carcinoma - Full Text View

Purpose

The purpose of this study is to evaluate efficacy, safety, and patient reported outcomes (PRO) of different regimens of transarterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC).

Condition	Intervention	Phase
Hepatocellular Carcinoma	Procedure: Transarterial chemoembolization (TACE)	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Factorial Assignment Masking: Single Blind (Subject) Primary Purpose: Treatment
Official Title:	The Efficacy, Safety, and Patient Reported Outcomes of Different Regimens of Transarterial Chemoembolization in Patients With Hepatocellular Carcinoma

Resource links provided by NLM:

MedlinePlus related topics: Cancer Liver Cancer

Drug Information available for: Ethiodized oil

U.S. FDA Resources

Further study details as provided by Sun Yat-sen University:

Primary Outcome Measures:

Overall survival [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Time to progression [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]

Enrollment:	365
Study Start Date:	July 2007
Study Completion Date:	December 2010
Primary Completion Date:	December 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: combined chemotherapy with embolization chemotherapy with lipiodol mixed with EADM 50mg, lobaplatin 50mg, and MMC 6mg, with particle embolization.	Procedure: Transarterial chemoembolization (TACE) drugs and dosage: chemotherapy with lipiodol mixed with EADM 50mg, lobaplatin 50mg, and MMC 6mg, plus particle embolization.
Experimental: combined chemotherapy without embolization chemotherapy with lipiodol mixed with EADM 50mg, lobaplatin 50mg, and MMC 6mg, without particle embolization.	Procedure: Transarterial chemoembolization (TACE) drugs and dosage: chemotherapy with lipiodol mixed with EADM 50mg, lobaplatin 50mg, and MMC 6mg.
Experimental: single agent chemotherapy with embolization chemotherapy with lipiodol mixed with EADM 50mg, plus particle embolization.	Procedure: Transarterial chemoembolization (TACE) Drugs and dosage:chemotherapy with lipiodol mixed with EADM 50mg, plus particle embolization.

Detailed Description:

Transarterial chemoembolization (TACE) has been recommended as first line non-curative therapy for non-surgical patients with large/multifocal HCC who do not have vascular invasion or extrahepatic spread. There has not been any standardized protocol in the choice of chemotherapeutic agents, dosage, dilution, rate of injection, and time interval between treatments. Similarly, there is no agreement on the choice of embolizing agents, degree of embolization, and whether the chemotherapeutic agent should be given together, or before the embolizing agent.

Comparison(s): In patients with HCC who underwent TACE therapy, stratified by whether they have vascular invasion and tumor size, we compare efficacy, safety, and patient reported outcomes (PRO) of different regimens of TACE.

Regimen 1: lipiodol combined chemotherapy with embolization

Regimen 2: lipiodol combined chemotherapy without embolization

Regimen 3: lipiodol single agent chemotherapy with embolization

Eligibility

Ages Eligible for Study:	18 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Adult patients with minimal height of 150cm and minimal weight of 50 KG
Histological confirmed HCC
with no previous treatment
With unresectable tumor
With solitary or multiple intrahepatic tumor, the diameter of the largest one must larger than 7cm.
No significant baseline liver dysfunction. Cirrhotic status of Child-Pugh class A only
No significant renal impairment (creatinine clearance < 30 mL/minute)
The following laboratory parameters:
- Platelet count ≥ 60,000/µL
- Hemoglobin ≥ 8.5 g/dL
- Total bilirubin ≤ 1.5 mg/dL
- ASL and AST ≤ 5 x upper limit of normal
- Serum albumin ≥ 35 g/L
- Serum creatinine ≤ 1.5 x upper limit of normal
- INR ≤ 1.5 or a Pt/PTT within normal limits
- Absolute neutrophil count (ANC) > 1,500/mm3
Ability to understand the protocol and to agree to and sign a written informed consent document

Exclusion Criteria:

Avascular tumor
Main portal vein obstruction without cavernous transformation
Evidence of hepatic decompensation including esophageal or gastric variceal bleeding or hepatic encephalopathy
Obstructive jaundice
Severe underlying cardiac or renal diseases
Known or suspected allergy to the investigational agent or any agent given in association with this trial
Pregnant or breast-feeding patients.
History of organ allograft
Active clinically serious infections
Any condition that is unstable or which could jeopardize the safety of the patient and his/her compliance in the study

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00493402

Locations

China, Guangdong
Cancer Center Sun Yat-sen University
Guangzhou, Guangdong, China, 510060

Sponsors and Collaborators

Sun Yat-sen University

Ministry of Health, China

Guangdong General Hospital

The 458 Hospital of Chinese PLA

Kaiping central hospital

Investigators

Principal Investigator:

Jin-Qing Li, M.D.

Cancer Center, Sun Yat-set University

More Information

Publications:

Bruix J, Sherman M. Management of hepatocellular carcinoma. Hepatology 2005; 42:1208-1236.

BREEDIS C, YOUNG G. The blood supply of neoplasms in the liver. Am J Pathol. 1954 Sep-Oct;30(5):969-77. No abstract available.

Llovet JM, Bruix J. Systematic review of randomized trials for unresectable hepatocellular carcinoma: Chemoembolization improves survival. Hepatology. 2003 Feb;37(2):429-42. Review.

Ono Y, Yoshimasu T, Ashikaga R, Inoue M, Shindou H, Fuji K, Araki Y, Nishimura Y. Long-term results of lipiodol-transcatheter arterial embolization with cisplatin or doxorubicin for unresectable hepatocellular carcinoma. Am J Clin Oncol. 2000 Dec;23(6):564-8.

Lau WY, Yu SC, Lai EC, Leung TW. Transarterial chemoembolization for hepatocellular carcinoma. J Am Coll Surg 2006; 202:155-168.

Lopez PM, Villanueva A, Llovet JM. Systematic review: evidence-based management of hepatocellular carcinoma--an updated analysis of randomized controlled trials. Aliment Pharmacol Ther. 2006 Jun 1;23(11):1535-47. Review.

Lai CL, Wu PC, Chan GC, Lok AS, Lin HJ. Doxorubicin versus no antitumor therapy in inoperable hepatocellular carcinoma. A prospective randomized trial. Cancer. 1988 Aug 1;62(3):479-83.

Hong K, Georgiades CS, Geschwind JF. Technology insight: Image-guided therapies for hepatocellular carcinoma--intra-arterial and ablative techniques. Nat Clin Pract Oncol. 2006 Jun;3(6):315-24. Review.

Trevisani F, De Notariis S, Rossi C, Bernardi M. Randomized control trials on chemoembolization for hepatocellular carcinoma: is there room for new studies? J Clin Gastroenterol. 2001 May-Jun;32(5):383-9. Review.

Kajanti M, Pyrhonen S, Mantyla M, Rissanen P. Intra-arterial and intravenous use of 4' epidoxorubicin combined with 5-fluorouracil in primary hepatocellular carcinoma. A randomized comparison. Am J Clin Oncol. 1992 Feb;15(1):37-40.

Heresbach D, Raoul JL, Bentue-Ferrer D, Bretagne JF, Van den Driessche J, Gastard J. [Chemotherapy combined with Lipiodol. In vitro study of the kinetics of release of adriamycin] Gastroenterol Clin Biol. 1989 Oct;13(10):775-8. French.

Higashi S, Shimizu M, Nakashima T, Iwata K, Uchiyama F, Tateno S, Tamura S, Setoguchi T. Arterial-injection chemotherapy for hepatocellular carcinoma using monodispersed poppy-seed oil microdroplets containing fine aqueous vesicles of epirubicin. Initial medical application of a membrane-emulsification technique. Cancer. 1995 Mar 15;75(6):1245-54.

Raoul JL, Heresbach D, Bretagne JF, Ferrer DB, Duvauferrier R, Bourguet P, Messner M, Gosselin M. Chemoembolization of hepatocellular carcinomas. A study of the biodistribution and pharmacokinetics of doxorubicin. Cancer. 1992 Aug 1;70(3):585-90.

Kasugai H, Kojima J, Tatsuta M, Okuda S, Sasaki Y, Imaoka S, Fujita M, Ishiguro S. Treatment of hepatocellular carcinoma by transcatheter arterial embolization combined with intraarterial infusion of a mixture of cisplatin and ethiodized oil. Gastroenterology. 1989 Oct;97(4):965-71.

Nakao N, Uchida H, Kamino K, Nishimura Y, Ohishi H, Takayasu Y, Miura K. Determination of the optimum dose level of lipiodol in transcatheter arterial embolization of primary hepatocellular carcinoma based on retrospective multivariate analysis. Cardiovasc Intervent Radiol. 1994 Mar-Apr;17(2):76-80.

Nakao N, Uchida H, Kamino K, Nishimura Y, Ohishi H, Takayasu Y, Nakamura H, Kuroda C, Fujita M, Yoshioka H, et al. Effectiveness of Lipiodol in transcatheter arterial embolization of hepatocellular carcinoma. Cancer Chemother Pharmacol. 1992;31 Suppl:S72-6.

Takayasu K, Shima Y, Muramatsu Y, Moriyama N, Yamada T, Makuuchi M, Hasegawa H, Hirohashi S. Hepatocellular carcinoma: treatment with intraarterial iodized oil with and without chemotherapeutic agents. Radiology. 1987 May;163(2):345-51.

Nakamura H, Hashimoto T, Oi H, Sawada S. Transcatheter oily chemoembolization of hepatocellular carcinoma. Radiology. 1989 Mar;170(3 Pt 1):783-6.

Konno T. Targeting cancer chemotherapeutic agents by use of lipiodol contrast medium. Cancer. 1990 Nov 1;66(9):1897-903.

Egawa H, Maki A, Mori K, Yamamoto Y, Mitsuhashi S, Bannai K, Asano K, Ozawa K. Effects of intra-arterial chemotherapy with a new lipophilic anticancer agent, estradiol-chlorambucil (KM2210), dissolved in lipiodol on experimental liver tumor in rats. J Surg Oncol. 1990 Jun;44(2):109-14.

Mathupala SP, Rempel A, Pedersen PL. Glucose catabolism in cancer cells: identification and characterization of a marked activation response of the type II hexokinase gene to hypoxic conditions. J Biol Chem. 2001 Nov 16;276(46):43407-12. Epub 2001 Sep 13.

Ramsey DE, Kernagis LY, Soulen MC, Geschwind JF. Chemoembolization of hepatocellular carcinoma. J Vasc Interv Radiol 2002; 13:S211-221.

Camma C, Schepis F, Orlando A, Albanese M, Shahied L, Trevisani F, Andreone P, Craxi A, Cottone M. Transarterial chemoembolization for unresectable hepatocellular carcinoma: meta-analysis of randomized controlled trials. Radiology. 2002 Jul;224(1):47-54. Review.

Llovet JM, Real MI, Montana X, Planas R, Coll S, Aponte J, Ayuso C, Sala M, Muchart J, Sola R, Rodes J, Bruix J; Barcelona Liver Cancer Group. Arterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial. Lancet. 2002 May 18;359(9319):1734-9.

Lo CM, Ngan H, Tso WK, Liu CL, Lam CM, Poon RT, Fan ST, Wong J. Randomized controlled trial of transarterial lipiodol chemoembolization for unresectable hepatocellular carcinoma. Hepatology. 2002 May;35(5):1164-71.

Homma H, Mezawa S, Doi T, Miyanishi K, Takada K, Kukitsu T, Oku T, Masuko E, Nojiri S, Niitsu Y. A comparative randomized trial of intermittent intrahepatic arterial carboplatin- versus doxorubicin-lipiodol emulsion in advanced hepatocellular carcinoma (stage IV). Hepatogastroenterology. 2004 Jul-Aug;51(58):1135-9.

Stuart K. Chemoembolization in the management of liver tumors. Oncologist. 2003;8(5):425-37. Review.

Geschwind JF, Ramsey DE, van der Wal BC, Kobeiter H, Juluru K, Hartnell GG, Choti MA. Transcatheter arterial chemoembolization of liver tumors: effects of embolization protocol on injectable volume of chemotherapy and subsequent arterial patency. Cardiovasc Intervent Radiol. 2003 Mar-Apr;26(2):111-7. Epub 2003 Mar 6.

Responsible Party:	Shi Ming, Dr., Sun Yat-sen University
ClinicalTrials.gov Identifier:	NCT00493402 History of Changes
Other Study ID Numbers:	hcc-001
Study First Received:	June 27, 2007
Last Updated:	December 12, 2012
Health Authority:	China: Ministry of Health

Keywords provided by Sun Yat-sen University:

Antineoplastic Agents
administration & dosage
Carcinoma, Hepatocellular
Chemoembolization, Therapeutic

Humans
Liver Neoplasms
therapy

Additional relevant MeSH terms:

Carcinoma
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Liver Neoplasms

Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 21, 2013

Different Regimens of Transarterial Chemoembolization for Hepatocellular Carcinoma (TACEforHCC)